Hemostatic Factors,APOL1 Risk Variants,and the Risk of ESRD in the Atherosclerosis Risk in Communities Study

Background and objectives

Hemostatic factors have been associated with kidney function decline, and evidence suggests stronger effects among African Americans. The presence of APOL1 renal risk variants, common in African Americans, might partly underlie this risk difference.

Design, setting, participants, & measurements

A total of 13,337 participants in the Atherosclerosis Risk in Communities study were followed from 1987–1989 until 2010. Participants were categorized into three groups by ancestry and APOL1 risk status: European Americans (n=10,206), African Americans with zero or one APOL1 risk allele (n=2,733), and African Americans with two APOL1 risk alleles (n=398). ESRD events were ascertained through linkage to the US Renal Data System. Cox regression was used to estimate the risk for ESRD associated with hemostatic factors (factor VIIc, factor VIIIc, fibrinogen, von Willebrand factor, protein C, and antithrombin III).

Results

There were 232 cases of ESRD over 21.5 years (European Americans, 119; African Americans with zero or one APOL1 risk allele, 94; African Americans with two APOL1 risk alleles, 19). In unadjusted and adjusted analysis of the overall population, higher levels of all hemostatic factors, except antithrombin III, were significantly associated with ESRD (all P<0.05). Factor VIIc had the strongest association (per one interquartile range; adjusted hazard ratio, 1.46; 95% confidence interval, 1.21 to 1.76). With the exception of fibrinogen, the risk associated with each hemostatic factor was stronger in African Americans with two APOL1 risk alleles compared with the other two groups. Statistically significant interactions were seen for factor VIIIc and protein C (interaction between those with two APOL1 risk allele and the other two groups: P<0.02 for factor VIIIc and <0.04 for protein C).

Conclusions

Higher levels of factor VIIc, VIIIc, fibrinogen, von Willebrand factor, and protein C were associated with ESRD risk, with a significantly stronger association of factor VIIIc and protein C in African Americans with two APOL1 risk alleles.     

Cardiovascular Risk and Psoriasis: Beyond the Traditional Risk Factors

Psoriasis is an autoimmune disease resulting in plaques of the skin. Similar to atherosclerosis, inflammation is integral to the initiation and propagation of plaque development. Mounting evidence has emerged demonstrating that psoriasis not only is associated with increased prevalence of cardiovascular risk factors, but also is an independent risk factor for the development of cardiovascular disease. Systemic therapies for moderate to severe psoriasis can increase the cardiovascular risk. Despite the evidence that psoriasis is an independent risk factor for cardiovascular disease, current guidelines only address managing traditional risk factors. An interdisciplinary approach is needed to find the necessary steps beyond classic risk reduction and detection of early cardiovascular disease in patients with psoriasis, as well as to develop a cardiovascular disease preventive regimen.     

Urinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities Study

Background and objectives

Liver fatty acid binding protein (L-FABP), kidney injury molecule 1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG), and neutrophil gelatinase–associated lipocalin (NGAL) are urinary markers of tubular injury that may also be markers of chronic kidney damage. We evaluated the association of these markers with incident ESRD in a community-based sample from the Atherosclerosis Risk in Communities Study.

Design, setting, participants, & measurements

This was a matched case-control study of 135 patients with ESRD and 186 controls who were matched on sex, race, kidney function, and diabetes status at baseline (Atherosclerosis Risk in Communities Study visit 4, 1996–1998). Urinary KIM-1 indexed to creatinine (Cr), NAG/Cr, NGAL/Cr, and L-FABP/Cr were measured in stored spot urine samples from the baseline examination. Associations of KIM-1/Cr, NAG/Cr, and NGAL/Cr with patients with incident ESRD through 2008 were modeled continuously and categorically (quartiles) using conditional logistic regression. L-FABP/Cr was modeled only categorically because of a large number of measurements below the lower limit of detection for the assay (2.4 ng/ml).

Results

No significant associations were observed for NAG/Cr, NGAL/Cr, or L-FABP/Cr with ESRD. Those in the highest category for KIM-1/Cr had a higher risk of ESRD compared with those with undetectable biomarker levels (reference group) in unadjusted models (odds ratio, 2.24; 95% confidence interval, 1.97 to 4.69; P=0.03) or adjustment for age (odds ratio, 2.23; 95% confidence interval, 1.06 to 4.67; P=0.03). This association was attenuated with additional adjustment for baseline kidney function (odds ratio, 2.02; 95% confidence interval, 0.95 to 4.31; P=0.07 after additional adjustment for eGFR and natural log of the urinary albumin-to-creatinine ratio). No association between KIM-1/Cr and ESRD was found when KIM-1/Cr was analyzed as a continuous variable.

Conclusions

Elevated urinary KIM-1/Cr may be associated with a higher risk of incident ESRD, but it does not add to risk prediction after accounting for traditional markers of kidney function in this population.     

Aldosterone and the Risk of Hypertension

Aldosterone, the key hormone in the mineralocorticoid pathway, plays a fundamental role in salt and water homeostasis, blood pressure regulation, and cardiovascular remodeling. Both genomic and nongenomic mechanisms influence aldosterone-induced renal sodium reabsorption. Furthermore, the mineralocorticoid receptors in nonepithelial tissues, including the heart and vascular smooth muscle cells, have recently been discovered. Thus, aldosterone likely has pleiotropic effects that contribute to the modulation of blood pressure. Among patients with hypertension in general, and among those with more severe or resistant hypertension in particular, a higher-than-expected prevalence of primary hyperaldosteronism is noted. Among individuals with resistant hypertension, aldosterone antagonists have also been shown to be effective in lowering blood pressure. Most significantly, recent community-based studies among non-hypertensive individuals in the general population have demonstrated that both higher serum aldosterone concentrations and a higher aldosterone to renin ratio portend a greater risk of developing hypertension. The combination of the aforementioned observations underscores the importance of the mineralocorticoid pathway in the pathogenesis of hypertension.     

Raloxifene and Risk for Stroke Based on the Framingham Stroke Risk Score

Purpose

Raloxifene reduces vertebral fracture and invasive breast cancer risks, but increases fatal strokes in postmenopausal women at increased coronary risk. We assessed whether this risk is concentrated in postmenopausal women already at high stroke risk.

Methods

Raloxifene Use for The Heart (RUTH) enrolled 10,101 postmenopausal women (mean age 67 years) with or at increased coronary heart disease risk; Multiple Outcomes of Raloxifene Evaluation (MORE) enrolled 7705 osteoporotic postmenopausal women (mean age 66 years). A Framingham Stroke Risk Score (FSRS) was calculated for all women with no prior cerebrovascular events (n = 16,858). The validity of the FSRS was assessed in the placebo groups, and then raloxifene-associated stroke risk was analyzed by FSRS subgroups.

Results

FSRS predicted an increased stroke risk in the placebo group of both clinical trials. There was no difference in the incidence of nonfatal strokes between the raloxifene and placebo groups in MORE or RUTH, regardless of baseline Framingham stroke risk. In RUTH, women with FSRS <13 showed no increase in raloxifene-associated fatal stroke risk (hazard ratio [HR] 1.08; 95% confidence interval [CI], 0.49-2.37). Those with FSRS ≥13 had a 75% increased risk of raloxifene-associated fatal stroke (HR 1.75; 95% CI, 1.01-3.02; interaction P = .33). In MORE, where 80% of women had a FSRS <13, no increase in fatal (HR 0.57; 95% CI, 0.19-1.68) stroke risk was observed.

Discussion

Risk of fatal stroke associated with raloxifene was greater in women at high stroke risk. These results might be useful for identifying postmenopausal women at high risk of first stroke who should avoid raloxifene therapy.     

Cholecystectomy and the Risk of Colorectal Adenomas

Cholecystectomy has been identified as a risk factor for colorectal cancer, yet little attention has been given to the relationship between cholecystectomy and colorectal adenomas. Utilizing data collected in two large cross-sectional studies of colorectal adenoma risk factors, we examined the association between cholecystectomy and colorectal adenomas. In the adjusted logistic regression model, both men and women showed no effect of cholecystectomy on risk of colorectal adenomas (men: OR 0.67 [95% CI 0.30–1.47]; women: OR 1.46 [95% CI 0.92–2.29]). No effect was seen when examining the time since cholecystectomy for men. There was a slight association found for women who had a cholecystectomy less than 10 years prior (OR 2.02 [95% CI 1.06–3.87]) but no association was seen in women with cholecystectomy at least 10 years prior (OR 1.14 [95% CI 0.62–2.09]). Thus, we conclude that, although cholecystectomy is a risk factor for colorectal cancer, cholecystectomy is not a risk factor for colorectal adenomas.     

关注他汀类药物所致的糖尿病风险

自高胆固醇血症被证实为心血管事件的主要危险因素以来,作为调脂药的他汀类药物在心血管疾病的一级和二级预防中的地位不断上升,目前已成为仅次于抗生素的第二大类临床用药。然而,伴随其临床使用的日益广泛,一些除肝毒性、肌毒性以外的不良反应也逐渐被发现并引起关注。美国食品药品监督管理局于2012年2月宣布,他汀类药物制造商需在其说明书中增加有关糖尿病风险的说明,同年12月,我国食品药品监督管理局也提出了类似风险的警示。目前,他汀类药物所致糖尿病风险已成为最受关注的不良反应之一。现就他汀类药物所致糖尿病风险的相关研究作一综述。     

Age and the Risk of Venous Thromboembolism

Journal of Thrombosis and Thrombolysis -     

Bladder Augmentation and the Risk of Carcinoma

Augmentation cystoplasty is the gold standard for increasing bladder capacity and improving bladder compliance in patients with refractory neurogenic bladder dysfunction. Significant long-term complications of this procedure do occur, however. The potential risk of bladder or bowel patch malignancy is concerning. The early literature has reviewed the associated risk involved with infectious sources of bladder dysfunction and augmentation. There is a paucity of data on outcomes of augmentation for noninfectious etiologies. This article reviews the pathophysiology, risk, and incidence rates as they correlate with bowel segment used, histology, risk factors, and screening recommendations for bladder augmentation–associated malignancies of noninfectious etiologies.     

Mapping the Risk of Yellow Fever Infection

The World Health Organization coordinated a comprehensive, systematic review of the countries and areas at risk for yellow fever (YF) virus transmission. The review applied the following evidence to each country and area considered: human and non-human YF cases, human serology for anti-YF antibody obtained prior to widespread YF vaccination, altitude, vegetation, and vector distribution. The result was the categorization of countries or areas as endemic, transitional, low potential for infection, or no risk. This information was adapted to create a map that defined the areas where vaccination against YF may be recommended. Travel health professionals, countries, and public health bodies can use this information as they determine recommendations and requirements for vaccination. This paper reviews the process and outcomes of the review of YF risk, and places it in the context of providing YF vaccination.